A Roadmap Toward the Definition of Actionable Tumor-Specific Antigens

Abstract

The search for tumor-specific antigens (TSAs) has considerably accelerated during the past decade due to the improvement of proteogenomic detection methods. This provides new opportunities for the development of novel antitumoral immunotherapies to mount an efficient T cell response against one or multiple types of tumors. While the identification of mutated antigens originating from coding exons has provided relatively few TSA candidates, the possibility of enlarging the repertoire of targetable TSAs by looking at antigens arising from non-canonical open reading frames opens up interesting avenues for cancer immunotherapy. In this review, we outline the potential sources of TSAs and the mechanisms responsible for their expression strictly in cancer cells. In line with the heterogeneity of cancer, we propose that discrete families of TSAs may be enriched in specific cancer types.

Tumour mutational burden: an overview for pathologists

“…Whether TMB is a good proxy for tumour immunogenicity is an open research question and the activities to develop more standardised ways of modelling cancer cell immunogenicity is an area of active research. 32,36 Future measures of TMB may integrate results from epitope prediction tools and also include neoantigens generated from non-coding regions of the genome from aberrant methylation. 36,37…”

“…32,36 Future measures of TMB may integrate results from epitope prediction tools and also include neoantigens generated from non-coding regions of the genome from aberrant methylation. 36,37…”

Integrating Cancer Vaccines in the Standard-of-Care of Ovarian Cancer: Translating Preclinical Models to Human

“…Single nucleotide variants (SNVs) that result from a single nucleotide substitution are commonly used for identifying tumor neoantigens. Other mutations, including frameshifts, insertion-deletions (indels) and chromosomal translocations can produce tumor neoantigens with higher affinities to HLA molecules caused by larger sequence divergences and should be investigated [110][111][112]. Targeting driver mutations that provide intrinsic tumor growth advantages may be important, as well as clonal or truncal tumor neoantigens expressed by every tumor cell [113].…”

The immunopeptidome from a genomic perspective: Establishing immune-relevant regions for cancer vaccine design

“…Here, we present a comprehensive and well-engineered resource of presented peptidic antigens (immunopeptidomes) that incorporates the full breadth of neoantigen science 17–21 . The immunopeptidome profiles of over 486 samples from 26 published cancer studies 22,23 were analyzed using a novel harmonized approach.…”